Markovnikov-addition of H-phosphonates to terminal alkynes under metal- and solvent-free conditions

An addition of H-phosphonates to aryl alkynes was realized under solvent- and metal-free conditions, affording Markovnikov-selective α-vinylphosphonates in moderate to good yields. A wide range of aryl alkynes could be applied for the reaction. A tentative mechanism of addition–substitution was proposed based on in situ31P {1H} NMR studies.

our delight, diethyl 1-phenyl ethenylphosphonate (3aa), a Markovnikov addition product, was obtained in high regioselectivity but in poor yield (10%). The reaction conditions were subsequently optimized with 1a and 2a. Considering Tf 2 O was moisture sensitive, all experiments were performed under nitrogen. Two equivalents 2a was used to ensure 1a was consumed as much as possible. The conversion and isolated yield were calculated based on 1a (Table 1).
When the mixture of 1a, 2a and Tf 2 O was stirred at room temperature, a new signal at 17.1 ppm was observed on 31 P NMR spectrum. The two doublet peaks at 6.35 and 6.17 ppm on proton NMR spectrum, assigned as 3aa, was detected in 12% (entry 1 of Table 1). The conversion of 1a was improved to 46% when the reaction was carried out at 40 C, and to 92% at 60 C (entries 2 and 3). At 65 C, the conversion was detected in 98%, and 3aa was isolated, whose structure was conrmed by NMR spectrum. 14 The conversion cannot be further improved at higher temperature such as 80 C.
When 0.5 equiv. Tf 2 O was used, the conversion of 1a was dropped to 79%. The usage of 0.8 equivalent of Tf 2 O led 92% conversion (entries 6 and 7). However, excessive Tf 2 O, such as 1.2 equivalents, resulted in the reduced conversion (86%, entry 8).
Once triic acid was used to replace Tf 2 O, 3aa was not detected (entry 9).
Adopting the above optimized condition, the reaction of alkyne with H-phosphonate was performed ( Table 2). Dimethyl phosphite 2b reacted with phenylacetylene to afford dimethyl 1phenylethenyl phosphonate 3ab in 43% yield, which was less than the reaction of 2a. Perhaps due to the bigger spatial hindrance, diisopropyl phosphite 2c did not reacted with 1a to    Table 3). Besides of 1a, aromatic alkynes possessing electron-donating groups smoothly reacted with 2a to afford corresponding 3ba-3ha in 17-62% yields. The low yield of 3ha may be ascribed to meta-methyl that had variable electronic effect. For chloro and bromo-substituted alkynes, 3ia and 3ja were afforded in 56% and 46% yields, respectively. Perhaps due to steric hindrance, the ortho-chlorophenyl ethyne gave lower yield of 3 than parasubstituted alkyne.
Some ethynyl heterocycles, such as 2-or 3-ethynylthiophene could be employed for the reaction, affording 3la or 3ma, respectively. For 1,4-diethynylbenzene (1n), the addition was realized when 2a and Tf 2 O were used in double equivalents. However, the alkynes having strong EWG, such as triuoromethyl or 3-pyridinyl, cannot react with 2a. Aliphatic terminal alkynes, such as 1-octyne, also did not afford the product.
The mechanism of the reaction was studied via in situ NMR experiments, and was proposed in Scheme 1. 2a and Tf 2 O formed triate 4 of phosphite via an equilibrium. 12b,15 Meanwhile, triic acid was generated (step 1). The addition of triic acid to 1a formed 1-phenylvinyl triate 5 as an intermediate (step 2). The subsequent nucleophilic substitution of 5 with 4 formed vinyl phosphonate 3aa (step 3).
The step 1 was conrmed by the observation of the signal of acidic proton in TfOH during the mixing of 2a with Tf 2 O (Fig. 1A). When 1a was added, 5 was detected, as seen the two doublet peaks at 5.61 and 5.38 ppm on 1 H NMR spectrum (step 2 and Fig. 1B). When the mixture was heated at 60 C, the signals of 3aa at 6.16-6.37 ppm emerged. The peaks were increased with prolonged heating, accompanied with the decreasing of the signals of 5 (step 3, Fig. 1C and D). Similar results were observed when Tf 2 O was initially mixed with 1a ( Fig. 1E-H). Aer heating at 60 C for 8 h, the signals of 1a, respected by the peak of terminal alkyne at 3.07 ppm, were disappeared (Fig. 1H).
The addition of triic acid to 1a probably formed a-carbon ion as intermediate, which could be stabilized by phenyl and be converted to Markovnikov-product 5. Although the nucleophilic substitution on vinyl carbon was difficulty, the strong leaving activity of triuoromethanesulfonyloxy on 5 enabled step 3 occurred. Miura proposed a cyclic phosphirenium intermediate for the addition and cyclization, 13 which could be probably stabilized by the alkyl groups of inner-alkynes and secondary phosphine oxides. In our case, the electron-withdrawing alkoxyl on phosphorus of 2a was not favorable for the formation of the phosphirenium, thus the reaction proceeded via a-carbon ion and addition-substitution occurred.
TfOH was necessary to the formation of 5 from 2a (step 2). However, triic acid cannot sole promote the reaction, as seen in entry 9 of Table 1. The results indicated the poor nucleophilic ability of 2a. Aer 2a was converted to P(III) species 4 by triic anhydride, the lone electron pair on phosphorus of 4 could attack 5 to form the product. It was not sure the small quartet peak at 4.62 ppm belonged to 4 (Fig. 1F). On 31 P NMR spectrum, the peak of 2a at 17.0 ppm obviously became broad in poor resolution when mixed with triic anhydride (as seen in ESI †). The results also supported the equilibrium between 2a and 4 (step 1).

Conclusions
In summary, a mild and convenient method to generate vinylphosphonates was developed. The method employed aryl  alkynes and H-phosphonates, was performed under metal-and solvent-free conditions, and afforded Markovnikov-adducts as single regio-isomer. This methodology was compatible with a wide range of aryl alkynes. On the basis of in situ 1 H NMR studies, an addition-substitution mechanism was proposed, which was different to the reported phosphirenium mechanism.

Conflicts of interest
There are no conicts to declare.